To deepen understanding of how cancers arise from normal cells and how they progress to form metastasis and become resistant to drug therapy; To identify genes that are instrumental in these events; To develop better strategies for intervening in the growth and survival of cancer cells. Over the past four decades---at the University of California-San Francisco, the National Cancer Institute, Memorial Sloan-Kettering Cancer Center, and, since late 2010, the National Human Genome Research Institute at the NIH--- my colleagues and I have tried to describe and understand the events that convert a normal cell into a cancer cell and thereby provide opportunities for better control of neoplastic diseases. These studies have been conducted with cultured cells, animal models (especially genetically engineered mice), and, increasingly in recent years, samples of human cancers and derived cell lines. We are opportunistic about the types of cancer we study, so our work has involved several tumor types, including adenocarcinomas of the lung, breast, and pancreas; sarcomas and brain tumors; and leukemias. Currently, most of our work is focused on lung cancers, especially lung adenocarcinomas, with an emphasis on discovering mutations and other changes that drive tumor behaviors, understanding the physiological consequences of those changes, and seeking ways to reverse them for therapeutic benefit. Collaborative projects Our group is involved in a variety of collaborations, most initiated before we arrived at the NIH and conducted largely in other laboratories. Most involve studies of lung carcinogenesis in our mouse models and have produced some of the publications in the list below. Further details are available upon request.